Histology

• Cell components


  • Plasma membrane
  • Transmembrane proteins/transport
  • Membrane organelles
• All tissues that make up organs are comprised of ECM and cells
• Cells are the basic structural and functional units, the smallest living parts of the body
• Eukaryotic


  Animal cells have nuclei surrounded by cytoplasm, which contains organelles and cytoskeleton
• Bacterial cells


  Lack nuclei and usually have cell walls around plasmalemma (plasma membrane)
• Differentiation


  Cells express sets of genes that mediate their cytoplasmic activities and make them more efficient in specialized functions
• Plasma membrane


  Also called cell membrane or plasmalemma, envelops every eukaryotic cell
• Plasma membrane composition


  • Phospholipids
  • Cholesterol
  • Proteins with oligosaccharide chains
• Plasma membrane


  • Functions as a selective barrier regulating the passage of materials into and out of the cell and facilitating the transport of specific molecules
  • Keeps ion content stable
  • Plays a key role in cell to environment interactions, by carrying out recognition and signaling functions
• Integrins


  Plasma membrane proteins linked to both cytoskeleton and ECM components to allow continuous exchange of influences, in both directions
• Plasma membrane thickness


  Ranges from 7.5 to 10 nm, therefore is only visible with electronic microscope
• Phospholipids


  Amphipathic (have both hydrophilic and hydrophobic parts)
• Plasma membrane structure


  Phospholipids arranged in double layer where fatty acid tails face each other (with cholesterol packed between them) while hydrophilic heads face out towards water
• Glycocalyx


  Outside the double layered plasma membrane, composed of glycolipids (lipids with sugar residue)
• Integral proteins


  Incorporated directly within the membrane
• Peripheral proteins


  Bound to one of the surfaces of the plasma membrane
• Plasma membrane proteins


  • Some protrude from either side and contribute to the glycocalyx, these protrusions are referred as receptors, which allow complex interactions such as cell adhesion, cell recognition, and the response to protein hormones
  • Their distribution is different on either side of the membrane, making it asymmetric
  • Some are not bound rigidly and can move, forming a fluid mosaic model of the membrane
  • Some that are part of larger enzyme complexes are usually less mobile and are located on specialized membrane patches termed lipid rafts
• Plasma membrane transport mechanisms

  • Diffusion
  • Channels
  • Carriers
  • Pumps
• Diffusion


  Small, nonpolar, lipophilic molecules directly cross the membrane readily
• Channels


  Multipass proteins that form pores that selectively pass ions (Na+, Ca+, K+) and small molecules. Water molecules pass through Aquaporins
• Carriers


  Transmembrane proteins that bind small molecules and move them via conformational changes
• Pumps


  Use active transport, utilizing energy from ATP and are often referred as ATPases
• Endocytosis


  Macromolecules (large) usually enter and exit the cell, while enclosed by part of plasma membrane (often after binding to a specific receptor). This forms a vesicle (bubble)
• Phagocytosis


  "cell eating" is when cells ingest particles (macrophages/neutrophils). When a foreign particle such as bacteria gets encircled by cell plasmalemma end cytoplasm, it gets entrapped in phagosome, which later merges with lysosome, which degrades everything within it
• Pinocytosis


  "cell drinking" similar event, but smaller in size and works on fluids. Sometimes these vesicles get transported to the opposite cell surface and get released – transcytosis
• Exocytosis


  • Triggered in many cells by transient increase in cytosolic Ca2+
  • Occurs via two pathways: Constitutive secretion, when release happens immediately after synthesis (e.g collagen fibers for ECM) and Regulated secretion, when release happens in response to outside signals (e.g. digestive enzymes)
  • Portions of cell membrane become part of endocytotic vesicles during endocytosis; during exocytosis, it is returned to the cell surface. This process is called membrane trafficking
• Cell communication


  Cells in a multicellular organism communicate to regulate tissue and organ development, to control their growth and division, and to coordinate their functions
• Gap junctions


  Adjacent cells form these to communicate
• Receptors


  Cells with receptors for specific ligand (transmitter) are called target cells
• Types of cell signaling

  • Endocrine signaling
  • Paracrine signaling
  • Autocrine signaling
  • Juxtacrine signaling
• Synaptic signaling


  A special type of paracrine interaction, neurotransmitters act on adjacent cells through special contact areas called synapses. This type of signaling is used by nerve endings and is very rapid and effective
• Receptor types


  • Channel-linked receptors
  • Enzymatic receptors
  • G protein–coupled receptors
• Signal transduction


  Ligands can be considered primary (first) messengers, which activate enzymes inside the cells. One such enzyme is adenyl cylcase, which generates large quantities of secondary messengers, some of which are cyclic adenosine monophosphate (cAMP), 1,2-diacylglycerol (DAG), inositol 1,4,5-triphosphate (IP3)
• Ribosomes


  20×30nm basophilic macromolecules made of rRNA (ribosomal). Function is to assemble proteins from amino acids carried by tRNA (Transporter), dictated by mRNA (messenger). Consists of two sub-units (30 and protein sub-units)
• Polyribosomes/Polysomes


  Multiple ribosomes binding same strand of mRNA
• Rough Endoplasmic Reticulum (RER)


  • Membranous network found in most cells, extends from surface of the nucleus throughout the cytoplasm and creates communicating channels (cisternae)
  • Surface is up to 30x of plasma membrane and is a major site of biosynthesis of proteins and lipids
  • Polyribosomes attached to some areas create rough and smooth ER
  • RER is prominent in cells that specialize in protein secretion
  • Has a highly regulate system to prevent nonfunctional proteins being forwarded to the pathway for secretion or to other organelles. Those that can't be assembled undergo ER-associated degradation (ERAD)
• Smooth Endoplasmic Reticulum (SER)

  • Regions of ER that lack polyribosomes
  • Continuous with RER, but is less abundant and not basophilic therefore can be viewed on TEM
  • Functions: 1. Synthesis of phospholipids and steroids 2. Contains enzymes for detoxification 3. Responsible for controlled release of Ca2+ which allows cells for rapid response, particularly well developed in muscle cells (sarcoplasmic reticulum)
• Golgi Apparatus


  • Completes posttranslational modifications of proteins produced in the RER and then packages and addresses these proteins to their proper destinations
  • Material moves to Golgi apparatus via transport veiscles, merges with it's cis face and gets carried to it's trans face where assambled products accumulate and eventually release
  • Forward movement of vesicles is mediated by coat protein COP-II while retrograde is mediated by COP-I
  • After transport the material get's stored in secretory granules until their release by exocytosis
• Lysosomes


  • Sites of intracellular digestion and turnover (reuse) of cellular components
  • Contain about 40 different hydrolytic enzymes and are particularly abundant in cells with great phagocytic activity (neutrophils, macrophages)
  • Enzymes have optimal activity at an acidic pH (~5.0) and are protected from the cytosolic pH (~7.2)
  • When lysosome fuses with the vesicle that has entered vie endocytosis it forms heterolysosome, which is larger and has heterogenous appearance due to its' contents. After which indigestable material is left as residual body
  • Some long-lived cells accumulate lipofuscin age pigment
• Proteasomes


  • Very small abundant protein complexes not associated with membrane, each approximately the size of the small ribosomal sub-unit
  • Function is to degrade denatured or otherwise nonfunctional polypeptides and remove proteins no longer needed by the cell
  • Cylindrical structure made of four stacked rings, each composed of seven proteins including proteases
  • At each end of the cylinder is a regulatory particle that contains ATPase and recognizes proteins with attached molecules of ubiquitin, an abundant cytosolic 76-amino acid protein found in all cells
  • Failure of proteasomes to function can cause an accumulation of defective proteins and eventually damages nervous system (Alzheimer and Huntington disease)